International Staging System for Multiple Myeloma

Abstract

There is a need for a simple, reliable staging system for multiple myeloma that can be applied internationally for patient classification and stratification. Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. Potential prognostic factors were evaluated by univariate and multivariate techniques. Three modeling approaches were then explored to develop a staging system including two nontree and one tree survival assessment methodologies. Serum beta₂-microglobulin (Sβ₂M), serum albumin, platelet count, serum creatinine, and age emerged as powerful predictors of survival and were then used in the tree analysis approach. A combination of Sβ₂M and serum albumin provided the simplest, most powerful and reproducible three-stage classification. This new International Staging System (ISS) was validated in the remaining patients and consists of the following stages: stage I, Sβ₂M less than 3.5 mg/L plus serum albumin ≥ 3.5 g/dL (median survival, 62 months); stage II, neither stage I nor III (median survival, 44 months); and stage III, Sβ₂M ≥ 5.5 mg/L (median survival, 29 months). The ISS system was further validated by demonstrating effectiveness in patients in North America, Europe, and Asia; in patients less than and ≥ 65 years of age; in patients with standard therapy or autotransplantation; and in comparison with the Durie/Salmon staging system. The new ISS is simple, based on easy to use variables (Sβ₂M and serum albumin), and recommended for early adoption and widespread use.